Diarrheal disease is an important cause of morbidity in infants and young children in developed countries and a major cause of morbidty and mortality in the same age group in developing countries. A major goal of this laboratory is the development of a rotavirus vaccine to prevent serious rotavirus disease in infants and young children. Two approaches that have been evaluated in humans: 1) the use of a live attenuated human rotavirus strain and 2) the use of a live rotavirus strain of animal origin. With reference to the first approach, we had observed that the tissue culture adapted mutant of human rotavirus (HRV) serotype 1 (Wa strain) was antigenic and attenuated in adult volunteers. The second approach, employing an animal rotavirus as vaccine has been applied successfully by Vesikari, et al,, using bovine rotavirus NCDV which was shown to be attenuated and to induce resistance to moderate or severe rotavirus diarrhea in infants and young children. We have performed extensive studies with another animal rotavirus, rhesus rotavirus (RRV) strain MMU18006, which was adapted to diploid simian FRhL-2 cells and which shares protective antigens with human rotavirus serotype 3. In addition, rhesus rotavirus (RRV) appears to be restricted in humans because it has not been recovered from persons undergoing rotavirus infection under natural conditions. In volunteer studies that began in adults and progressed stepwise to infants 4 months of age, RRV was found to be quite antigenic. However, transient fever and loose stools were observed in young vaccinees less than 1 year of age who received 1,000,000 pfu of RRV. However, infants 4-11 months old who were fed a 100,000 or 10,000 pfu of RRV in Venezuela did not develop fever or diarrhea. 100,000 pfu of RRV induced rotavirus antibodies in the serum of 82% of vaccinees. Further studies with this vaccine are planned.